Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo -: art. no. e109

被引:268
作者
Minakuchi, Y
Takeshita, F
Kosaka, N
Sasaki, H
Yamamoto, Y
Kouno, M
Honma, K
Nagahara, S
Hanai, K
Sano, A
Kato, T
Terada, M
Ochiya, T
机构
[1] Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 1040045, Japan
[2] Sumitomo Pharmaceut Co Ltd, Formulat Res Labs, Osaka 5670878, Japan
[3] Waseda Univ, Sch Educ, Dept Biol, Tokyo 1690051, Japan
[4] Koken Biosci Inst, Tokyo 1150051, Japan
关键词
D O I
10.1093/nar/gnh093
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Silencing gene expression by siRNAs is rapidly becoming a powerful tool for the genetic analysis of mammalian cells. However, the rapid degradation of siRNA and the limited duration of its action call for an efficient delivery technology. Accordingly, we describe here that Atelocollagen complexed with si RNA is resistant to nucleases and is efficiently transduced into cells, thereby allowing long-term gene silencing. Site-specific in vivo administration of an anti-luciferase siRNA/Atelocollagen complex reduced luciferase expression in a xenografted tumor. Furthermore, Atelocollagen-mediated transfer of siRNA in vivo showed efficient inhibition of tumor growth in an orthotopic xenograft model of a human non-seminomatous germ cell tumor. Thus, for clinical applications of siRNA, an Atelocollagen-based nonviral delivery method could be a reliable approach to achieve maximal function of siRNA in vivo.
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页数:7
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